An incursion made by an Iranian drone into Israeli air space prompted the Israel Air Force to scatter eight fighter jets in a coordinated assault on the "T-4 base" in Syria - the base reportedly responsible for the drone launch.
"Israel's face is turned toward peace, but we will continue to defend ourselves with determination against any attack on us and against any Iranian attempt to base itself in Syria or anywhere else", Netanyahu said.
Both pilots ejected and were injured, one critically.
The regime said it intercepted the missiles and destroyed a lot of them, according to SANA.
Israeli planes then struck an Iranian installation in Syria from which, the Israeli military said, the unmanned aircraft had been operated.
"This is the beginning of a new strategic era which puts an end to the violation of Syrian airspace and territory", Hezbollah announced via a statement published by Lebanon's ANI news agency, according to the Times of Israel.
He also noted that after decades during which Israeli warplanes were operating unmolested in Syria's airspace, the downing of one plane was to be expected, statistically.
"The Syrians are playing with fire when they allow the Iranians to attack Israel from their soil", said Lt. Col. Jonathan Conricus, a spokesman for the Israeli military, in a statement.
The large-scale offensive was apparently created to physically limit Syrian dictator Bashar Assad's ability to attempt such an attack against Israeli aircraft in the future, and to make him consider what a larger Israeli aerial assault would do to his military.
Israel's Brig. Gen. Ronen Manelis indicated that Iran's recent move was reckless, foolish and irresponsible.
Conricus said it was intercepted well inside Israel, north of the city of Beit Shean, near the Jordan border.
Israeli soldiers inspect the remains of an Israeli F-16 fighter jet that crashed near the northern Israeli Kibbutz of Harduf, on February 10, 2018.
Netanyahu spoke with both Russian President Vladimir Putin and US Secretary of State Rex Tillerson after Saturday's confrontation.
The Syrian Observatory for Human Rights said the Israeli airstrikes had killed at least six Syrian troops and allied militiamen.
A Turkish helicopter was shot down as the country continued its offensive against Kurdish fighters in northern Syria.
The joint operations room, run by Syria, Iran, Russia and Hezbollah, said the aircraft was on a regular mission gathering intelligence on fighters of the Islamic State of Iraq and the Levant (ISIL, also known as ISIS). Israel, which considers Iran its most potent enemy in the region, has been lobbying world powers - so far, apparently, without success - to distance these forces from the border areas. An Israeli F-16 was hit by Syrian anti-aircraft fire and its two crew bailed out over Israeli territory.
"Israel is our closest security partner in the region and we fully support Israel's inherent right to defend itself against threats to its territory and its people", said U.S. Defense Department spokesman Adrian Rankine-Galloway, adding that the U.S. was not involved in Israel's military response in Syria.
"It is necessary to unconditionally respect the sovereignty and territorial integrity of Syria and other countries in the region".